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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Fukuhara, Shigetomo Mochizuki, Naoki Moriya, Takahiro Nakahata, Norimichi Obara, Yutaro Ando, Koji |
| Description | Author Affiliation: Ando K ( Department of Cell Biology, National Cerebral and Cardiovascular Center Research Institute, Suita, Osaka 565-8565, Japan.) |
| Abstract | Reorganization of the actin cytoskeleton is responsible for dynamic regulation of endothelial cell (EC) barrier function. Circumferential actin bundles (CAB) promote formation of linear adherens junctions (AJs) and tightening of EC junctions, whereas formation of radial stress fibers (RSF) connected to punctate AJs occurs during junction remodeling. The small GTPase Rap1 induces CAB formation to potentiate EC junctions; however, the mechanism underlying Rap1-induced CAB formation remains unknown. Here, we show that myotonic dystrophy kinase–related CDC42-binding kinase (MRCK)-mediated activation of non-muscle myosin II (NM-II) at cell–cell contacts is essential for Rap1-induced CAB formation. Our data suggest that Rap1 induces FGD5-dependent Cdc42 activation at cell–cell junctions to locally activate the NM-II through MRCK, thereby inducing CAB formation. We further reveal that Rap1 suppresses the NM-II activity stimulated by the Rho–ROCK pathway, leading to dissolution of RSF. These findings imply that Rap1 potentiates EC junctions by spatially controlling NM-II activity through activation of the Cdc42–MRCK pathway and suppression of the Rho–ROCK pathway. |
| ISSN | 00219525 |
| e-ISSN | 15408140 |
| Journal | The Journal of Cell Biology |
| Issue Number | 6 |
| Volume Number | 202 |
| Language | English |
| Publisher | Rockefeller University Press (United States) |
| Publisher Date | 2013-09-16 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Actins Metabolism Cell Membrane Human Umbilical Vein Endothelial Cells Intercellular Junctions Myosin Type II Telomere-Binding Proteins Blotting, Western Cell Adhesion Cell Movement Cell Proliferation Cells, Cultured Cytology Immunoenzyme Techniques Genetics Myotonin-Protein Kinase Phosphorylation Protein-Tyrosine Kinases Antagonists & Inhibitors RNA, Small Interfering Cdc42 GTP-Binding Protein Rho GTP-Binding Proteins Rho-Associated Kinases Research Support, Non-U.S. Gov't Cell Biology |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Medicine |
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